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ACTIVE NOT RECRUITING

NCT04468984

PHASE3

Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet Versus Best Available Therapy to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis

Sponsor: AbbVie

View on ClinicalTrials.gov

Summary

Myelofibrosis (MF) is a rare blood cancer, notable for scarring of the bone marrow (the spongy tissue inside bones) and the spleen becoming larger. The purpose of this study is to assess safety and change in spleen volume when navitoclax is given in combination with ruxolitinib, compared to best available therapy, for adult participants with MF. Navitoclax is an investigational drug (not yet approved) being developed for the treatment of MF. Participants in this study will be randomly selected (like picking numbers out of a hat) to be in 1 of 2 treatment arms. Neither participants nor the study doctor will be able to pick which treatment arm a participants enters. In Arm A, participants will receive navitoclax in combination with ruxolitinib. In Arm B, participants will receive the best available therapy (BAT) for MF. In Arm C, participants will receive navitoclax. Adult participants with a diagnosis of MF that came back or did not get better after earlier treatment will be enrolled. Approximately 330 participants will be enrolled in approximately 322 sites across the world. In Arm A, participants will receive navitoclax tablet by mouth once daily with by mouth ruxolitinib tablet twice daily. In Arm B, participants will receive the BAT available to the investigator. In Arm C, participants will receive navitoclax tablet by mouth once daily. Participants will receive the study drug until they experience no benefit (determined by the investigator), participants cannot tolerate the study drugs, or participants withdraw consent. The approximate treatment duration is about 3 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.

Official title: Randomized, Open-Label, Phase 3 Study Evaluating Efficacy and Safety of Navitoclax in Combination With Ruxolitinib Versus Best Available Therapy in Subjects With Relapsed/Refractory Myelofibrosis (TRANSFORM-2), Incorporating Extension Arm C - Continued Access for Navitoclax to Roll Over Subjects From Studies M10-166, M16-109, M16-191, and M19-753

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

330

Start Date

2020-08-31

Completion Date

2026-12

Last Updated

2026-01-09

Healthy Volunteers

Conditions

Myelofibrosis (MF)

Interventions

DRUG

Navitoclax

Tablet; Oral

DRUG

Ruxolitinib

Tablet; Oral

DRUG

Best Available Therapy (BAT)

Tablet/Capsule; Oral or Solution for Subcutaneous Injection

Inclusion Criteria: * Must complete the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of the 7 days immediately prior to the date of randomization and must agree to collect MFSAF data daily by ePRO device during the study collection window. \-- Has at least 2 symptoms each with an average score \>= 3 or an average total score of \>= 12, as measured by the MFSAF v4.0. * Documented diagnosis of primary myelofibrosis (MF) as defined by the World Health Organization (WHO) classification, post polycythemia vera (PPV)-MF, or post essential thrombocytopenia (PET)-MF, characterized by bone marrow fibrosis grades 2 or 3. * Classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+). * Must currently be on treatment or have received prior treatment with a single Janus Kinase 2 (JAK2) inhibitor, ruxolitinib, and meet one of the following criteria (in addition to the minimum splenomegaly and symptom burden also required for eligibility): * Treatment with ruxolitinib for \>= 24 weeks that was stopped due to lack of spleen response (refractory), or loss of spleen response or symptom control after a previous response (relapsed), or was continued despite relapsed/refractory status. * Treatment with ruxolitinib for \< 24 weeks with documented disease progression while on therapy as defined by any of the following: * Appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM) in participants with no evidence of splenomegaly prior to the initiation of ruxolitinib. * A \>= 100% increase in the palpable distance below the LCM in participants with measurable spleen distance 5 to 10 centimeters (cm) prior to the initiation of ruxolitinib. * A \>= 50% increase in the palpable distance below the LCM in participants with measurable spleen distance \> 10 cm prior to the initiation of ruxolitinib. * A spleen volume increase of \>= 25% (as assessed by Magnetic Resonance Imaging \[MRI\] or Computed Tomography \[CT\] scan) in participants with a spleen volume assessment prior to the initiation of ruxolitinib. * Prior treatment with ruxolitinib of at least 10 mg twice daily (BID) for \>= 28 days with intolerance defined as new RBC transfusion requirement (at least 2 units/month for 2 months) while receiving a total daily ruxolitinib dose of \>= 30 mg but unable to reduce dose further due to lack of efficacy. Note: Participant must not require a ruxolitinib dose less than 10 mg BID (20 mg daily) due to prior history of ruxolitinibrelated ≥ Grade 3 toxicity. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. * Splenomegaly defined as palpable spleen measurement \>= 5 cm below left costal margin or spleen volume \>= 450 cm3 as assessed centrally by MRI or CT scan. * Baseline platelet count \>= 100 × 10\^9/L. Exclusion Criteria: * Received prior treatment with a B-cell lymphoma 2 homology 3 (BH3)-mimetic compound, bromodomain and extra-terminal (BET) inhibitor, phosphoinositide 3- kinase and telomerase inhibitors (e.g., parsaclisib), prior use of \> 1 JAK2 inhibitor or stem cell transplant. * Eligible for stem cell transplantation at the time of study entry. * Receiving medication that interferes with coagulation or platelet function within 3 days prior to the first dose of study drug or during the study treatment period except for low dose aspirin (up to 100 mg daily) and low molecular weight heparin (LMWH). * Receiving anticancer therapy for an active malignancy or MF including chemotherapy, radiation therapy, hormonal therapy such that at least 5 half-lives of that medication is completed at least 7 days prior to the first dose of study drug or within 30 days prior to first dose of study drug, whichever is shorter, and during the study treatment period (other than any overlapping therapy as part of the selected BAT).

Locations (229)

Ironwood Cancer & Res Ctr /ID# 222162

Chandler, Arizona, United States

Highlands Oncology Group, PA /ID# 221826

Springdale, Arkansas, United States

City of Hope /ID# 218996

Duarte, California, United States

Providence - St. Jude Medical Center /ID# 271382

Fullerton, California, United States

Moores Cancer Center /ID# 271596

La Jolla, California, United States

Moores Cancer Center at UC San Diego /ID# 219009

La Jolla, California, United States

Long Beach Memorial Medical Ct /ID# 224542

Long Beach, California, United States

Icri /Id# 221967

Whittier, California, United States

St. Mary's Hospital Regional Cancer Center /ID# 224229

Grand Junction, Colorado, United States

Augusta University Georgia Cancer Center /ID# 219051

Augusta, Georgia, United States

Columbus Regional Research Institute /ID# 224410

Columbus, Georgia, United States

University of Chicago Medical Center /ID# 271373

Chicago, Illinois, United States

Northwest Oncology & Hematology - Elk Grove Village /ID# 222818

Elk Grove Village, Illinois, United States

Loyola University Medical Ctr /ID# 219048

Maywood, Illinois, United States

Indiana Blood & Marrow Transpl /ID# 221587

Indianapolis, Indiana, United States

Tulane Medical Center - New Orleans /ID# 222940

New Orleans, Louisiana, United States

Duplicate_Ochsner Clinic Foundation-New Orleans /ID# 222777

New Orleans, Louisiana, United States

American Oncology Partners of Maryland /ID# 222836

Bethesda, Maryland, United States

Dana-Farber Cancer Institute /ID# 218998

Boston, Massachusetts, United States

University of Michigan /ID# 218463

Ann Arbor, Michigan, United States

Henry Ford Hospital /ID# 221190

Detroit, Michigan, United States

William Beaumont Hospital /ID# 222705

Royal Oak, Michigan, United States

Saint Louis University Cancer Center /ID# 222287

St Louis, Missouri, United States

Summit Medical Group-Florham Park /ID# 222620

Florham Park, New Jersey, United States

Hackensack Univ Med Ctr /ID# 219047

Hackensack, New Jersey, United States

The Cancer Institute at St. Francis Hospital /ID# 231782

Greenvale, New York, United States

Manhattan Hematology Oncology MHO Associates /ID# 223193

New York, New York, United States

Memorial Sloan Kettering Cancer Center-Koch Center /ID# 221081

New York, New York, United States

Atrium Health Wake Forest Baptist Medical Center /ID# 222899

Winston-Salem, North Carolina, United States

MetroHealth Medical Center /ID# 222650

Cleveland, Ohio, United States

Pennsylvania Cancer Specialists & Research Institute /ID# 271376

Gettysburg, Pennsylvania, United States

Hospital of the University of Pennsylvania /ID# 219001

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center /ID# 223955

Philadelphia, Pennsylvania, United States

Texas Oncology - Abilene - Antilley Road /ID# 271379

Abilene, Texas, United States

Duplicate_Houston Methodist Hospital /ID# 223103

Houston, Texas, United States

University of Texas Health San Antonio MD Anderson Cancer Center /ID# 233942

San Antonio, Texas, United States

Utah Cancer Specialists Salt Lake Clinic /ID# 221962

Salt Lake City, Utah, United States

Virginia Cancer Specialists - Fairfax /ID# 223016

Fairfax, Virginia, United States

Providence Everett /ID# 223130

Everett, Washington, United States

Yakima Valley Memorial Hosp /ID# 224368

Yakima, Washington, United States

HSHS St. Vincent Hospital /ID# 224468

Green Bay, Wisconsin, United States

The Kinghorn Cancer Centre /ID# 221097

Darlinghurst, New South Wales, Australia

Border Medical Oncology Research Unit Albury Wodonga Regiona /ID# 223848

East Albury, New South Wales, Australia

Calvary Mater Newcastle /ID# 224324

Waratah, New South Wales, Australia

The Alfred Hospital /ID# 221096

Melbourne, Victoria, Australia

Royal Perth Hospital /ID# 221099

Perth, Western Australia, Australia

Universitaetsklinikum St. Poelten /ID# 221709

Sankt Pölten, Lower Austria, Austria

Medizinische Universitaet Graz /ID# 220919

Graz, Styria, Austria

Ordensklinikum Linz GmbH Elisabethinen /ID# 220914

Linz, Upper Austria, Austria

Klinikum Wels-Grieskirchen GmbH /ID# 220915

Wels, Upper Austria, Austria

Medizinische Universitaet Wien /ID# 220911

Vienna, Vienna, Austria

Hanusch Krankenhaus /ID# 220912

Vienna, Austria

ZAS Cadix /ID# 221468

Antwerp, Antwerpen, Belgium

Cliniques Universitaires UCL Saint-Luc /ID# 224221

Brussels, Brussels Capital, Belgium

Grand Hôpital de Charleroi - Les Viviers /ID# 224827

Charleroi, Hainaut, Belgium

UZ Gent /ID# 220841

Ghent, Oost-Vlaanderen, Belgium

Vitaz /Id# 228150

Sint-Niklaas, Oost-Vlaanderen, Belgium

AZ-Delta /ID# 221469

Roeselare, West-Vlaanderen, Belgium

UMHAT Alexandrovska EAD /ID# 231652

Sofiya, Sofia, Bulgaria

UMHAT Dr Georgi Stranski EAD /ID# 231650

Pleven, Bulgaria

Acibadem City Clinic Tokuda University Hospital EAD /ID# 231649

Sofia, Bulgaria

UMHAT Sveti Ivan Rilski /ID# 231651

Sofia, Bulgaria

UMHAT Sveta Marina /ID# 234119

Varna, Bulgaria

Juravinski Cancer Centre /ID# 220887

Hamilton, Ontario, Canada

Ottawa Hospital Research Institute /ID# 238858

Ottawa, Ontario, Canada

University Health Network_Princess Margaret Cancer Centre /ID# 253942

Toronto, Ontario, Canada

CISSS-CA (Centre Integre de sante et de services sociaux de Chaudiere-Appalache) /ID# 222433

Lévis, Quebec, Canada

McGill University Health Centre - Glen Site /ID# 222614

Montreal, Quebec, Canada

CHUQ- Hôpital de l'Enfant-Jesus /ID# 220888

Québec, Quebec, Canada

Clinical Hospital Dubrava /ID# 230801

Zagreb, City of Zagreb, Croatia

Klinicka bolnica Merkur /ID# 230799

Zagreb, City of Zagreb, Croatia

Klinicki bolnicki centar Zagreb /ID# 230798

Zagreb, City of Zagreb, Croatia

Klinicki bolnicki centar Osijek /ID# 231503

Osijek, County of Osijek-Baranja, Croatia

Klinicki Bolnicki Centar (KBC) Split /ID# 230800

Split, Split-Dalmatia County, Croatia

Fakultní Nemocnice Brno - Jihlavská /ID# 220959

Brno, Brno-mesto, Czechia

Vseobecna fakultni nemocnice v Praze /ID# 220969

Prague, Czechia

Aalborg University Hospital /ID# 224391

Aalborg, North Denmark, Denmark

Roskilde Sygehus /ID# 224456

Roskilde, Region Sjælland, Denmark

Duplicate_CHU DE NICE-HOPITAL LARCHET II /ID# 256291

Nice, Alpes-Maritimes, France

CHU NIMES - Hopital Caremeau /ID# 219128

Nîmes, Gard, France

Centre Hospitalier Universitaire de Bordeaux /ID# 222696

Pessac, Gironde, France

CHU de Nantes, Hotel Dieu -HME /ID# 219127

Nantes, Pays de la Loire Region, France

HCL - Hopital Lyon Sud /ID# 222695

Pierre-Bénite, Rhone, France

Centre Hospitalier Métropole Savoie - Site Hôpital de Chambéry /ID# 223771

Chambéry, Savoie, France

Chu Angers /Id# 219129

Angers, France

Hôpital Saint-Louis /ID# 221390

Paris, France

Hopital Avicenne - APHP /ID# 221287

Bobigny, Île-de-France Region, France

Universitatsklinikum Mannheim /ID# 221529

Mannheim, Baden-Wurttemberg, Germany

Stauferklinikum Schwaebisch Gmuend /ID# 223948

Mutlangen, Baden-Wurttemberg, Germany

Gemeinschaftspraxis Dr. Heinrich und Prof. Bangerter /ID# 225025

Augsburg, Bavaria, Germany

Universitaetsmedizin Rostock /ID# 224157

Rostock, Mecklenburg-Vorpommern, Germany

Augusta-Kranken-Anstalt gGmbH, Bochum-Mitte /ID# 224695

Bochum, North Rhine-Westphalia, Germany

Klinikum Chemnitz gGmbH /ID# 224575

Chemnitz, Saxony, Germany

BAG Freiberg-Richter, Jacobasch, Illmer, Wolf /ID# 221346

Dresden, Saxony, Germany

OncoResearch Lerchenfeld GmbH /ID# 225034

Hamburg, Germany

Klinikum rechts der Isar /ID# 221526

Munich, Germany

Olympion General Clinic /ID# 261423

Pátrai, Achaia, Greece

General Hospital of Athens Laiko /ID# 221175

Athens, Attica, Greece

General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 221179

Athens, Greece

University General Hospital of Patras /ID# 221178

RION Patras Achaia, Greece

And 129 more locations on ClinicalTrials.gov

Clinical Research Directory

Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet Versus Best Available Therapy to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (229)